Background. ABO and Rh(D) phenotyping of both blood donors and transfused patients is routinely performed by blood banks to ensure compatibility. These analyses are done by antibody-based agglutination assays. However, blood is not routinely tested for minor blood group antigens on a regular basis because of cost and time constraints. This can result in alloimmunization of the patient against one or more minor antigens and may complicate future transfusions. Study design and Methods. To address this problem, we have generated an assay on the GenomeLab SNPstream genotyping system (Beckman Coulter, Fullerton, CA) to simultaneously test polymorphisms linked to 22 different blood antigens using donor’s DNA isolated from minute amounts of white blood cells. Results. The results showed that both the error rate of the assay, as measured by the strand concordance rate, and the no-call rate were very low (0.1%). The concordance rate with the actual red blood cell and platelet serology data varied from 97 to 100%. Experimental or database errors as well as rare polymorphisms contributing to antigen conformation could explain the observed differences. However, these rates are well above requirements since phenotyping and cross-matching will always be performed prior to transfusion. Conclusion. Molecular profiling of blood donors for minor red blood cell and platelet antigens will give blood banks instant access to many different compatible donors through the set-up of a centralized data storage system.